Liver fibrosis is associated with fatal liver diseases such as liver cancer and liver cirrhosis. For preventing common liver diseases, diagnosis and therapy of liver fibrosis at an early stage is important. Activated hepatic stellate cells (HSCs) play important roles in liver fibrosis. In damaged liver, HSCs change their characters from the steady state to the active state, and induce secretion of cytokines and growth factors from hepatocytes and nonparenchymal cells. Activated HSCs also produce extracellular matrix (ECM)-constituting factors such as collagen, which contribute to liver fibrosis. Thus, targeting to activated HSCs, and delivery of a gene or agent to activated HSCs are key points of therapy of liver fibrosis.
Recently, the present inventors discovered that a polymer containing N-acetylglucosamine (GlcNAc) has strong binding ability to vimentin and desmin on the cell surface (Non-patent Documents 1 and 2). Further, the present inventors reported that an N-acetylglucosamine-containing polymer (PVGIcNAc) can identify vimentin- and desmin-positive cells from a hepatocyte population. The N-acetylglucosamine-containing polymer interacts with vimentin-positive cells such as sinusoidal endothelial cells, Kupffer cells and HSCs. In particular, activated HSCs more strongly express vimentin and desmin than HSCs in the steady state and other nonparenchymal cells. PVGIcNAc is a polymer having a structure in which N-acetylglucosamine is bound to a polystyrene backbone. The hydrophobic polystyrene chain is strongly adsorbed to a polystyrene culture dish, which is also hydrophobic. Taking advantage of this property, selective culture of specific hepatocytes became possible by preparing a PVGlcNAc-coated culture dish.
The indocyanine green (ICG) fluorescent dye is approved by FDA, and widely used for imaging and therapy of diseases. ICG has also been used for evaluation of liver function by measurement of its blood level. However, in cases where ICG alone is injected, the ICG fluorescence signal rapidly disappears from blood. In order to realize ICG imaging that can be maintained for a long period, its binding with a nanomaterial is necessary. Polymers and phospholipids have been used for stabilizing ICG in blood.
Delivery of small interfering ribonucleic acid (siRNA) is hopeful as a therapeutic method for diseases, which method is based on knockdown of a specific disease-associated gene or protein. However, degradation by enzymes, as well as incapability of siRNA to pass through the cell membrane are problematic. In order to solve these problems, many researchers have studied stable delivery systems for delivering siRNA to cells or a tissue by a method using a virus vector (for example, adenovirus or lentivirus) or a method using no virus vector (using, for example, liposomes, a cation polymer or a dendrimer).